This research proposal seeks to critically examine the basis for the definitions of neonatal hypoglycemia which guide current practice and to further define the pathophysiologic mechanisms responsible for the high incidence of hypoglycemia. The validity of current definitions of hypoglycemia will be tested by examining whether the ranges of glucose levels which have been used to define the statistical normal for neonates are altered by the way infants are fed. This will be achieved by prospective studies of the effect of early feeding on plasma glucose levels in groups of small-for-gestational-age and appropriate-for-gestational-age newborn infants. We have found evidence that two processes required for fasting glucose homeostasis are limited at birth: ketogenesis and gluconeogenesis. These observations will be extended by examining the roles of glucagon and carnitine in the maturation of the ability of newborns to synthesize ketone bodies. The site at which hepatic ketogenesis is limited will be tested by seeing whether neonates are able to utilize medium chain triglycerides for ketone synthesis. The patency of the gluconeogenic pathway in newborn infants will be tested at different levels by the administration of various glucose precursors to localize the rate limiting step. Neonates with persistent hypoglycemia will be studied to describe the mechanism of the hypoglycemia and the effects of treatment with glucocorticoids.